Treating incontinence by injecting muscle stem cells

This not-yet-available in the US treatment for urinary incontinence may be of interest to many in the group…

Beth (with multiple system atrophy)) had another interesting post recently on an MSA-related list. I’ve gotten her permission again to copy it below.

She includes an abstract from a 5/21/06 American Urological Association meeting. The abstract summarizes two clinical studies done in Austria and Canada on injecting muscle stem cells to treat urinary incontinence. Roger Dmochowski, MD, a professor with the Dept of Urology at Vanderbilt University in Nashville, moderated a press conference on urinary incontinence at the meeting. He said two interesting things:

* “The technique is minimally invasive compared to surgical treatments for urinary incontinence. Once it gets traction, it could go rapidly into the practice arena.”

* Some larger studies will be beginning very soon in the United States.

If you want to keep an eye out for possible trials in the US, you can: 1) watch and search on clinicaltrials.org, using “urinary incontinence” as the search term, 2) watch Medscape’s weekly newsletters, and 3) go to a medical library or go online to review announcements put out by major urology journals.

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From: Beth Klitch
Date: Tue May 30, 2006 6:01pm(PDT)
Subject: Exciting new treatment for urinary incontinence – Injection of muscle stem cells

Urinary incontinence is another common condition that we MSA patients experience. Some of us respond to medications such as Flomax that reduce the bladder spasms that can cause urge incontinence. Some of us may undergo surgery to have devices such as Medtronic’s InterStim device implanted to send electrical signals to the sacral nerves that help stimulate the bladder to contract. Many more of us find ourselves isolated or fearful of incontinence accidents and thus we pass up opportunities to travel outside our homes or to visit friends.

Earlier this month, the American Urological Association met and heard reports about a wide range of topics that affect the urinary tract. I have included an extended summary of some exciting research that is underway to treat and actually cure urinary incontinence. Note that the first two clinical studies were performed in Austria and Canada and that larger trials are planned for the United States in upcoming months. This may be an opportunity to volunteer to take part in a clinical trial that has high potential to improve the quality of our lives. Also note that the results were significantly better for women than men and that there are some risks to any surgical procedures, even ones that are minimally invasive.

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May 22, 2006 (Atlanta) ­ Injection of muscle stem cells into the suburethral mucosa may be effective for the treatment of urinary incontinence, according to findings from 2 clinical studies. Hannes Strasser, MD, from the Universitatsklinik fur Urologie, Medizinische Universitat Innsbruck, Austria, and colleagues reported their findings here at the American Urological Association 2006 Annual Meeting.

Injecting stem cells into the urethral submucosa is expected to alleviate atrophy of the submucosa by potentially boosting the contractility of the muscle tissue and improving urethral function. In the study, a total of 130 patients (45 men and 85 women) with stress or mixed urinary incontinence were treated with transurethral ultrasound­guided injections. Patients were aged 36 to 85 years. Changes in morphology and function of the urethra and rhabdosphincter and quality of life were evaluated.

While under local anesthesia, patients had small skeletal muscle biopsies taken from their upper arm. Cells from the sample were cultured, and fibroblasts were eventually mixed with about 2.5 mL of collagen, which served as carrier material. With the aid of a transurethral ultrasound probe and injection device, the fibroblasts were introduced into the urethral submucosa. The myoblasts were directly injected into the rhabdosphincter to reconstruct the muscle.

Urinary incontinence was cured after injection of stem cells in 111 (79 women, 32 men) of the 130 patients. Therapy was able to increase the thickness of the urethra and the rhabdosphincter as well as increase the activity and contractility of the rhabdosphincter. An additional 17 patients experienced an improvement but not complete relief of incontinence.

Significant improvements in quality of life were also observed after treatment, and the therapy appeared to be well tolerated. No adverse effects or complications were observed. Dr. Strasser noted that further follow-up indicated that 1 patient had a major complication ­ a perforation in a male patient who had undergone several surgeries and radiation therapy.

According to Dr. Strasser, the efficacy of this technique is better in women than men, possibly for 2 reasons: the injection is easier in women due to the shorter length of the urethra. The second is that after radical prostatectomy in men, changes such as scarring can take place in the urethra. “In females the efficacy rate is more than 90%, whereas in males the efficacy rate is about 72% to 73%,” he told Medscape.

The therapeutic effect appeared to be long-lasting. “The full effect of the therapy takes about 3 to 4 weeks to achieve, whereas other injectable therapies can take effect immediately,” he said. “However, the vast majority of patients who do well 3 months after therapy remain stable. These patients are still continent, meaning they don’t need pads.”

A smaller, North American study evaluating a similar procedure was reported by Lesley K. Carr, MD, from the University of Toronto, Ontario, Canada, and colleagues. Six women, aged 41 to 66 years, with stress urinary incontinence, were treated with either a trans- or periurethral injection technique; one of the patients was reinjected after 6 months.

Skeletal muscle tissue was taken from each patient with a needle biopsy technique. Muscle-derived cells were then isolated and expanded in culture. After at least 1 month of follow-up, no improvement was observed in patients treated with a smaller (8 mm) cystoscopic injection needle. However, 2 subsequent transurethral injections using a longer needle (10 mm) and the 2 periurethral injections did result in improvement in 4 patients, who all reported an improvement in quality of life.

“We hypothesize that the injected muscle-derived cells differentiated into new muscle fibers and improved muscle function, but the exact mechanisms of these actions are still being investigated,” note Dr. Carr and colleagues in their abstract. “Improvements to the delivery technique may have contributed to a greater success rate in the most recently injected patients.” Again, no adverse effects were noted.

Roger Dmochowski, MD, a professor with the Department of Urology at Vanderbilt University in Nashville, Tennessee, noted that the results seen with this technique are “very encouraging,” although he pointed out that various injection techniques and different types of cells are being studied, “making it difficult to compare results.”

Several centers in Europe are experimenting with autologous muscle stem cell injection, and some larger studies will be beginning very soon in the United States, noted Dr. Dmochowski, who moderated a press conference on urinary incontinence at the meeting. “The technique is minimally invasive compared to surgical treatments for urinary incontinence,” Dr. Dmochowski added. “Once it gets traction, it could go rapidly into the practice arena.”

AUA 2006 Annual Meeting: Abstracts 328 and 1284. Presented May 21, 2006.

Drug treatment for orthostatic hypotension

This will likely be of interest to the MSA folks or those with orthostatic hypotension as a symptom….

Beth Klitch has MSA. She lives in the Midwest. She posted this recently on an MSA digest; it’s about the success seen by Japanese researchers using an FDA-approved diabetes drug to treat post-prandial hypotension. I asked her permission to copy the post here because I think it may be useful to some of our group members.

To find the three-sentence Neurology journal article abstract the post below refers to, go to www.neurology.org and search for “voglibose.”

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From: Beth Klitch
Date: Tue May 30, 2006 5:44pm(PDT)
Subject: Exciting new use of an existing drug to treat hypotension after meal

Since many of us with MSA suffer from severe orthostatic hypotension, me included, I keep a close eye on research reports about medications and other treatments that may be available to help us treat this condition. Just a few days ago, an interesting report surfaced in Neurology 2006;66:1432-1434 about a drug primarily used to treat diabetes, but which has profound implications to help treat the hypotension that occurs right after eating a meal, also called post-prandial hypotension. Note that MSA patients were included in this research along with Parkinson’s patients and patients with diabetes.

I have shared the article summary below for those who are interested. I think this is potentially great news for us because it is another example of an existing drug that can be extended to treat an additional condition and has already met the FDA’s safety and efficacy standards. The drug is called Voglibose, is marketed as Volix, and is considered one of the most important alpha-glucosidase inhibitors. It works in treating diabetes by delaying the digestion and absorption of carbohydrates, thereby decreasing the rise in glucose levels and insulin levels that typically occur after eating a meal.

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NEW YORK (Reuters Health) May 24 – The alpha-glucosidase inhibitor voglibose can help reduce postprandial hypotension, Japanese researchers report in the May 9th issue of Neurology. Lead investigator Dr. Takahiro Maruta of Kanazawa University and colleagues note that reduced blood pressure after a meal is common in the elderly and in those with conditions such as Parkinson’s disease and diabetes mellitus. It can increase the risk of falls and coronary events.

To examine the effect of voglibose on postprandial hypotension, the researchers studied 48 elderly subjects including those with Parkinson’s disease, multiple system atrophy and diabetes as well as elderly and younger controls with no autonomic disorder. Within 2 hours of 75-g glucose loading, blood pressure fell by more than 20 mm Hg in 72.7% of the Parkinson’s patients, all of those with multiple system atrophy, 27.3% of the patients with diabetes, 23% of the elderly controls and none of the younger controls.

Following voglibose administration, there was a significant reduction in this drop in blood pressure. Without voglibose the mean drop was 41.5 mm Hg; with voglibose, it was 21.0 mm Hg. There was also a reduction in the duration of postprandial hypotension under the two conditions (52.3 minutes versus 17.3 minutes).

Summing up Dr. Maruta told Reuters Health, “Many people suffer from symptoms due to hypotension. Our research should cast some light on ways to help them.”

“Depression, Delirium & Dementia” – lecture notes

Stanford University (stanford.edu) sponsored a 3-part series on geriatric health in May.  The first evening, May 11, 2006, included this lecture:

“Depression, Delirium & Dementia: What Should We Be Doing?”
Speaker:  Barbara Sommer, MD, Asst Prof of Psychiatry and Behavioral Sciences, Stanford Univ

Local support group member Karen D. gave me her notes on the lecture.  This post attempts to summarize some of the key points in that lecture.

Robin


Dr. Sommer stated that life expectancy increases are not due to doctors but to infrastructure changes, such as indoor plumbing.

She stated that 27% of people older than 60 living in a community have some degree of depression.  Depressed people have two times the number of doctors’ appointments than others.  75% of elderly suicides have seen their doctors in the last month.  The rate of elderly white males is increasing.  Elderly women’s suicide rates drop to zero after they stop caregiving for their elderly spouses!

Of those with dementia, 64% have AD, 25% have Vascular Dementia, and 12-15% have Frontotemporal Dementia (FTD).

She mentioned that there are several drugs on the market to treat AD:  three acetylcholinesterase inhibitors (including Aricept) and Namenda.  The standard treatment is to prescribe one of the acetylcholinesterase inhibitors and add Namenda.  Glutamate is essential to the brain.  Namenda restores the glutamate levels to normal.

Dr. Sommer said that memory can be optimized through mental gymnastics, dance and tai-chi, avoiding medication that affects the brain, diet, avoiding obesity, avoiding stress, and optimizing near vision.

Medication that affects the brain includes some anticholinergics, benzodiazepams or sleeping pills, antihistamines, etc.

Those with a higher BMI (body mass index) have a higher risk of dementia. She pointed out that when you lose near vision, you lose stimulation and the ability to participate in activities.  Bottom line – lose weight and see your optometrist!

Dr. Sommer repeatedly noted the negative effects of stress.

Dr. Sommer said that delirium is reversible.  She distributed an article on “Preventing delirium in older people,” published 7/15/05 in the British Medical Bulletin.  You can find an abstract of the article online at no charge:

bmb.oxfordjournals.org/cgi/content/abstract/73-74/1/25

The article states that:

“Up to 50% of delirium affecting older people develops after admission to (the) hospital.  These cases often result from hospital-related complications or inadequate care.” 

The paper focuses on how to prevent the delirium that is acquired in the hospital and is preventable.

 

“Cognitive Changes w/Aging” and “Maintaining Health” – lecture notes

Stanford sponsored a 3-part series on geriatric health in May. The second evening, May 18, 2006, included two lectures:

“Cognitive Changes With Aging: How Much Is Too Much?”
Speaker: Michael Greicius, MD, MPH, Dept of Neurology, Memory Disorders, Stanford Univ

“The Big Picture of Maintaining Health — Medications, Tests and Safety At Home”
Speaker: Yusra Hussain, MD, Dept of Internal Med, Geriatrician, Stanford Hospital & Clinics

This email attempts to summarize some of the key points in those lectures and provide a web link to the handout.

Dr. Greicius said that one-tenth of people over 65 have Alzheimer’s Disease. One-third of people over 85 have AD. 70% of the dementia cases are AD. The most common non-AD dementias are Vascular Dementia, FTD, and LBD. According to the “nun study,” the more education you have, the less impaired you are than someone with less education for the same degree of AD.

There is a disorder known as Mild Cognitive Impairment (MCI). Half of those with MCI convert to AD every four years. Scientists are looking into who will convert and how this can be prevented. Neither Vitamin E nor Aricept helped treat MCI.

There are many reversible causes of memory loss including B12 deficiency, low thyroid, medication (anticholinergics including some medications for urinary incontinence, beta-blockers, enzodiazepines, opiates, anti-epileptics, some medications for neuropathy), depression, alcohol, and retirement.

In general, people in their 50s and 60s can handle less than half the alcohol they could handle in their 30s.

There are some cognitive IMPROVEMENTS with normal aging: emotionality, semantic knowledge (knowledge of the world), and vocabulary.

Dr. Greicius spoke about cognitive decline with normal aging. Related to that topic, he distributed an article from the journal Nature Review Neuroscience, Feb ’04, titled “Insights into the Ageing Mind: A View from Cognitive Neuroscience.” He said this was an excellent review of the topic. An abstract of the article can be found at: (The full article costs $30.)
http://www.nature.com/nrn/journal/v5/n2/abs/nrn1323_fs.html

What can be done to minimize cognitive decline? His guesses include living healthy, moderate alcohol consumption, and no cigarettes. He explored the possible role of NSAIDs and cognitive training in minimizing decline.

His recommendations include: all things in moderation; minimize cardiovascular risk factors; sell your TV; read, dance, exercise; spend more time with friends and family; participate in medical research. Two journals did a review of ginkgo biloba studies. They showed no benefit. He doesn’t recommend taking extra Vitamin E.

Dr. Greicius said that there is a GRAIN of truth only to the layperson’s notion that for the clock test (part of the 4-hours of neuropsychological testing) those with AD can draw the clock and those with LBD cannot. He said that generally speaking those with LBD have visuospatial impairment early on, which is why they can’t draw the clock. But not all those with LBD have visuospatial impairment at the time of diagnosis. Another point: those with late stages AD can’t draw the clock either.

Dr. Hussain said that most people get a serious chronic condition at the age of 55. These can include geriatric syndromes, which are urinary incontinence, MCI, and depression.

If you think your health is excellent, you will live longer. If you think your health is merely good, your lifespan is normal/average.

About half of all deaths are attributable to preventable factors.

A healthy lifestyle includes: maintaining social life; being active each day; eating well; avoiding tobacco and excessive alcohol intake; following up on periodic health examinations and screening tests.

The best diet is rich in fruits, vegetables, whole grains, and nuts. One should have moderate consumption of polyunsatured fatty acids, omega 3 fatty acids, protein and dairy. One should have low consumption of carbs and animal fats. She does not recommend taking a multi-vitamin with antioxidants as a supplement. She says that antioxidants should be part of the diet.

In order to maintain cognitive function, she said that the “nun study” shows that it’s important to have a purpose in life and to stay busy with family and friends.

Frailty cannot be reversed.

That’s it! I didn’t attend the third lecture nor was I very interested in it so I won’t be emailing out notes from that one.

Regards,
Robin

Caregiving for those with Dementia – Class Notes

This post will be of interest to those who are caring for people with dementia…

I attended the 4-week class on caregiving for those with dementia at Avenidas in Palo Alto this month (May ’06). The class, called “It Takes Two: Dealing with Dementia-related Behavior,” was run by the Family Caregiver Alliance (caregiver.org), an SF-based organization that offers classes, resources, and counseling to those throughout the SF Bay Area and nationally.

A Dementia Fact Sheet was handed out. It states:

“[The] term ‘dementia’ is used by the medical community to describe patients with impaired intellectual capacity… Signs of dementia include short-term memory loss, inability to think problems through or complete complex tasks without step-by-step instructions, confusion, difficulty concentrating and paranoid, inappropriate or bizarre behavior. Clinical depression also may accompany early signs of dementia.”

In the first class, we discussed dementia. I think I wrote these statistics down correctly:
* 10% of people older than 65 have AD or dementia
* over the age of 85, almost 50% of the people have AD or dementia

There are reversible dementias and irreversible ones. The importance of getting a diagnosis was made clear by the fact that some dementias are reversible. In the first class, different diseases with dementia components were discussed, beginning with AD. LBD and PSP were both discussed.

Though it was not distributed, I think this publication summarizes the information presented the first day of class:

www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=569

Lots of FCA-authored materials were handed out at the first class, including:

1. Dementia – Fact Sheet: I can’t find this on their website. It lists possible causes of dementia (deteriorating intellectual capacity) including reactions to medications, emotional distress, metabolic disturbances, nutritional deficiencies, etc.

2. Alzheimer’s Disease – Fact Sheet: this is available on their website at:

www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=567

The fact sheet breaks AD into three stages and describes the dementia-related behaviors of each stage.

Note that the Dementia with Lewy Bodies – Fact Sheet on their website is woefully out of date. I’d suggest getting the latest info from the LBDA website. In particular, this brochure is excellent for caregivers, MDs, etc:

www.lewybodydementia.org/docs/brochure/3_brochure.pdf

3. Tips for Interacting with a Person with Dementia: I can’t find this on their website. The tips are:
* Reassure, reassure, reassure
* Try to remain calm
* Do not disagree with made up stories
* Give compliments often
* Respond to the person’s feelings, not their words
* Use distractions
* Do not try to reason with the person
* Give yourself permission to alter the truth
* Avoid asking questions that rely on short term memory
* Break down all tasks into simple steps
* Respond calmly to anger, don’t contradict or argue

4. Tips on Interacting with Persons with Alzheimer’s Disease or other Dementias (pages 1-3) and Qualities of Friendship in Relation to Someone with Dementia (page 4). I can’t find this on their website.

5. Principles for Understanding and Communicating with a Person with Dementia. I can’t find this on their website. The five principles are:
* Knowing and accepting the cognitive limitations of the person will help you set realistic expectations of the person’s behavior.
* Understand that OUR thoughts, attitude, and actions significantly impact on the behavior of the person with dementia.
* Recognize that behavior, even in a confused person, more likely results from a cause. It is triggered.
* Learn that to enhance communication with a person with dementia requires a commitment to remain “connected” regardless of the content of the conversation.
* Understand that changing behavior takes time, effort, and patience. Reward yourself often for working towards change.

6. A Reference List for Families and Professionals – Caring for Individuals with Dementia: I can’t find this on their website. It’s a list of books on family caregiving and dementia care.

7. Caring for Adults with Cognitive and Memory Impairments – Fact Sheet: this is available on their website at:

www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=392

The other three classes are hard to summarize. Basically we discussed and role-played communication strategies based on the tips and principles listed above.

This class will certainly be taught again in the Bay Area. It was taught in April in SF, I believe. And then the May class was in Palo Alto. My guess is that it will be taught again in the fall. You can check in periodically with the FCA’s website listing of classes to learn what’s available:

www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=1001

Regards,
Robin